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Neonatal diseases I
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Other medications used to attempt to treat apnea of prematurity include carnitine and doxapram. Carnitine deficiency can be a cause of apnea in infants and adults but no trial has shown that supplementation with carnitine made a difference in the frequency of apnea (9,10). Doxapram is another respiratory stimulant that has been used to treat apnea of prematurity. Doxapram must be administered intravenously, however, and potentially has the following side effects: seizures, liver dysfunction, and gastrointestinal irritation, which has limited its use. In a recent Cochrane review that compared the use of doxapram versus methylxanthine in the treatment of apnea found no difference between the two medications (11).
Medicines in neonates
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
The recommended dosage is 0.5 mg/kg/h to 1.5 mg/kg/h for the maintenance intravenous dose [31,33,37]. A loading dose of 3 mg/kg may be given [33]. The mean plasma concentrations obtained with these dosages range from 1.3 to 3.1 mg/1. Doxapram may be given orally by nasogastric tube over 1 hour, at a dose calculated as the daily intravenous dose of more than 50% [40], which leads to plasma concentrations within the therapeutic range [42]. To our knowledge, the only doxapram formulation marketed currently is the intravenous formulation (also used for the oral route), containing chlorbutanol as preservative.
Paper 5 Answers
Published in James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal, Get Through, 2014
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal
Doxapram is used as a respiratory stimulant in patients with acute-on-chronic respiratory failure and postoperative respiratory depression. It may also be used in the treatment of laryngospasm and postoperative shivering. The drug acts primarily by stimulating the peripheral chemoreceptors and has a secondary direct action on the respiratory centre. Doxapram is only available in a parenteral preparation and acts quickly following an intravenous bolus dose of 1 mg·kg−1. It has an onset of action of 20 seconds, peaks at 2 minutes and has a duration of action of 12 minutes.
Clostridioides difficile: innovations in target discovery and potential for therapeutic success
Published in Expert Opinion on Therapeutic Targets, 2021
Tanya M Monaghan, Anna M Seekatz, Benjamin H Mullish, Claudia C. E. R Moore-Gillon, Lisa F. Dawson, Ammar Ahmed, Dina Kao, Weng C Chan
Impaired innate and adaptive immune responses have been implicated in disease severity [119–123], and treatments focused on inducing immune responses relevant to C. difficile clearance and recovery from CDI represent novel treatment options. Three non-antibiotic FDA-approved drugs, amoxapine (an antidepressant), doxapram (a breathing stimulant), and trifluoperazine (an antipsychotic), were demonstrated to significantly protect against experimental CDI in a mouse model by reducing bacterial burden and toxin levels. RNA-seq data indicated that these drugs can promote disease alleviation through increased expression of several innate immune response-related genes previously demonstrated to impact CDI, including those involved in the recruitment of neutrophils, the production of interleukin 33 (IL-33), and the IL-22 signaling pathway [124]. While the specific mechanism of action is unknown, experimental data suggest that the use of innate immunity to combat C. difficile occurs indirectly via the gut microbiota, and IL-33-mediated disease alleviation was dependent on the presence of the microbiota [124].
Enteral broad-spectrum antibiotics antagonize the effect of fecal microbiota transplantation in preterm pigs
Published in Gut Microbes, 2021
Anders Brunse, Simone Margaard Offersen, Josefine Juliane Mosegaard, Ling Deng, Peter Damborg, Dennis Sandris Nielsen, Per Torp Sangild, Thomas Thymann, Duc Ninh Nguyen
Animal experimental procedures were approved by the Danish Animal Experiments Inspectorate (license number, 2014–15-0201-00418), which is in accordance with the guidelines from Directive 2010/63/EU of the European Parliament. Seventy-six crossbred piglets [(Landrace x Large white) x Duroc mixed donor semen] were delivered by cesarean section at ~90% gestation (day 106 ± 1) from three healthy sows. Briefly, sows were premedicated (1 mg/kg tiletamin, 1 mg/kg zolazepam, 0.4 mg/kg butorphanol) and surgical anesthesia was induced and maintained with propofol and 2% isoflurane inhalation. A uterine incision was made, and fetuses removed after ligating and transecting the umbilical cords. Once delivered, the newborn animals were housed in ventilated, preheated (37°C) individual incubators with initial oxygen supply (1–2 l/min). For resuscitation, animals received Doxapram (0.1 ml/kg im.), Flumazenil (0.1 ml/kg im.), physical stimulation and positive airway pressure ventilation until respiration had stabilized. Animals were then fitted with umbilical (4 Fr gauge) and orogastric (6 Fr gauge) catheters, and administered an 8 h continuous intra-arterial infusion of 16 ml/kg sow plasma to compensate for the lack of transplacental immunoglobulin transfer. Pigs were stratified according to gender and birth weight and randomly allocated to four groups (CON-CON, AB-CON, AB-FMT and CON-FMT), initially receiving antibiotic treatment (AB) or control treatment (CON), followed by FMT or control treatment (CON) in a 2 x 2-factorial experiment.